The purpose of this grant is to bring a variety of scientific disciplines to bear on a number of specific drug abuse problems. We propose to carry out major projects in the areas of chemical receptor probes, narcotic agonists and antagonists, the active principles of marihuana and methododlogy development. In the area of chemical receptor probes, we plan to synthesize specific compounds for studies of the postulated "cough", PCP, sigma agonist, nicotine, and THC receptors. In the narcotic areas, we plan to extend our studies toward the elucidation of the "cough" and sigma agonist receptors. We will continue to pharmacologically characterize opiate agonists and antagonists from our synthetic and drug abuse programs. Our studies with the cannabinoids will concentrate on assessing the dependence potential of Delta9-THC, the active principle of marihuana. We also plan to detemrine whether there are specific anatomical sites in the brain responsible for the typical behavioral effects of the cannabinoids. We plan to develop methods for better evaluating the rreinforcing efficacy of drugs of abuse. That is, why do some drugs act as more powerful reinforcers of behavior than others and what can we do to alter this? We will use cocaine as the first drug in these studies.